The role of soluble factors produced by lymphocytes and monocytes in controlling the activation, proliferation and differentiation of lymphocytes participating in immunological functions was studied. Studies were performed with B and T lymphocytes to establish the requirement of various soluble factors (interleukins) for the induction of immunoglobulin synthesis and the development of cytotoxic lymphocytes. B-cells. Supernatants derived from a cloned murine T-cell hybridoma line induced the proliferation and differentiation of purified B-cells stimulated with soluble anti Mu. Column chromatography of the supernatant distinguished these two activities based on M.W. The larger M.W. material induced proliferation but no Ig synthesis while the smaller M.W. material induced both activities. Subsequent studies showed that this "interleukin-like" activity was due solely to Mycoplasma hyorhinis contamination of the T-cell hybridoma and was not a function of the hybridoma cells. T-cells. The activation of resting T-cells to cytotoxic lymphocytes (CTL) by lectins or alloantigens is dependent on the presence of interleukins. The induction of CTL by the lectin, leukogglutinin, is dependent on the presence of only interleukin-2 (IL-2). Alloantigen induction of CTL is also dependent on IL-2 but requires in addition other soluble factors contained in supernatants derived from simulated El-4 cells. The significance of these studies is that soluble factors play an ever increasing critical role in regulating lymphocyte activity. Characterization of these pharmacologically active substances and their role(s) in establishing immune function are important aspects in the understanding of the immune system.